This is a new project undertaken to elucidate biochemical and immunological aspects of myelin disorders associated with neuro-AIDS including myelin pallor, vacuoler myelopathy and multifocal demyelination in the CNS as well as demyelinating peripheral neuropathy. Specific areas to be investigated fall into three categories: 1) Postmortem CNS tissue from AIDS patients will be analyzed for quantitative and qualitative alterations of myelin proteins for comparison to results previously obtained in other demyelinating diseases. Adjacent sections of tissue will be examined histologically and immunocytochemically to evaluate the pathological changes for correlation with the biochemical data. Preliminary biochemical results have already demonstrated a loss of myelin proteins in some areas of AIDS CNS; 2) Since the myelin associated glycoprotein (MAG) and the CD4 receptor for HIV are both in the immunoglobulin superfamily and have a modest, but statistically significant, sequence homology, possible interactions between MAG and GP120 will tested. The capacity of GP120 to interfere with the normal role of MAG in glia-axon interactions will be studied as will the possible role of MAG as a neural cell receptor for HIV. The effects of GP120 on cultured oligodendrocytes will also be examined. 3) Since high levels of antibodies to gangliosides and other glycoconjugates were previously detected in patients with some types of neuropathy (including a few that were HIV-positive), a larger number of sera from AIDS patients with neuropathy will be examined systematically for antibodies to glycoconjugates.
